scholarly journals Regulation of glycine metabolism by the glycine cleavage system and conjugation pathway in mouse models of non‐ketotic hyperglycinemia

2020 ◽  
Vol 43 (6) ◽  
pp. 1186-1198
Author(s):  
Kit‐Yi Leung ◽  
Sandra C. P. De Castro ◽  
Chloe Santos ◽  
Dawn Savery ◽  
Helen Prunty ◽  
...  
Keyword(s):  
Mouse Models ◽  
Glycine Cleavage System ◽  
Glycine Metabolism ◽  
Glycine Cleavage

scholarly journals mTORC1 activity regulates post-translational modifications of glycine decarboxylase to modulate glycine metabolism and tumorigenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rui Liu ◽  
Lin-Wen Zeng ◽  
Rong Gong ◽  
Fanen Yuan ◽  
Hong-Bing Shu ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Ubiquitin Ligase ◽  
Glycine Decarboxylase ◽  
Glycine Cleavage System ◽  
Sirtuin 3 ◽  
Post Translational Modifications ◽  
Mechanistic Target Of Rapamycin ◽  
Glycine Metabolism ◽  
Key Enzyme ◽  
Glycine Cleavage

AbstractGlycine decarboxylase (GLDC) is a key enzyme of glycine cleavage system that converts glycine into one-carbon units. GLDC is commonly up-regulated and plays important roles in many human cancers. Whether and how GLDC is regulated by post-translational modifications is unknown. Here we report that mechanistic target of rapamycin complex 1 (mTORC1) signal inhibits GLDC acetylation at lysine (K) 514 by inducing transcription of the deacetylase sirtuin 3 (SIRT3). Upon inhibition of mTORC1, the acetyltransferase acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes GLDC K514 acetylation. This acetylation of GLDC impairs its enzymatic activity. In addition, this acetylation of GLDC primes for its K33-linked polyubiquitination at K544 by the ubiquitin ligase NF-X1, leading to its degradation by the proteasomal pathway. Finally, we find that GLDC K514 acetylation inhibits glycine catabolism, pyrimidines synthesis and glioma tumorigenesis. Our finding reveals critical roles of post-translational modifications of GLDC in regulation of its enzymatic activity, glycine metabolism and tumorigenesis, and provides potential targets for therapeutics of cancers such as glioma.

scholarly journals GcsR, a TyrR-Like Enhancer-Binding Protein, Regulates Expression of the Glycine Cleavage System in Pseudomonas aeruginosa PAO1

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Zaara Sarwar ◽  
Benjamin R. Lundgren ◽  
Michael T. Grassa ◽  
Michael X. Wang ◽  
Megan Gribble ◽  
...  
Keyword(s):  
Metabolic Flux ◽  
Target Genes ◽  
Transcriptional Regulator ◽  
Glycine Cleavage System ◽  
Cellular Functions ◽  
Content Type ◽  
Founding Member ◽  
Expression Of Genes ◽  
Glycine Metabolism ◽  
Glycine Cleavage

ABSTRACT Glycine is required for various cellular functions, including cell wall synthesis, protein synthesis, and the biosynthesis of several important metabolites. Regulating levels of glycine metabolism allows P. aeruginosa to maintain the metabolic flux of glycine through several pathways, including the metabolism of glycine to produce other amino acids, entry into the trichloroacetic acid cycle, and the production of virulence factors such as hydrogen cyanide. In this study, we characterized GcsR, a transcriptional regulator that activates the expression of genes involved in P. aeruginosa PAO1 glycine metabolism. Our work reveals that GcsR is the founding member of a novel class of TyrR-like EBPs that likely regulate glycine metabolism in Pseudomonadales. Glycine serves as a major source of single carbon units for biochemical reactions within bacterial cells. Utilization of glycine is tightly regulated and revolves around a key group of proteins known as the glycine cleavage system (GCS). Our lab previously identified the transcriptional regulator GcsR (PA2449) as being required for catabolism of glycine in the opportunistic pathogen Pseudomonas aeruginosa PAO1. In an effort to clarify and have an overall better understanding of the role of GcsR in glycine metabolism, a combination of transcriptome sequencing and electrophoretic mobility shift assays was used to identify target genes of this transcriptional regulator. It was found that GcsR binds to an 18-bp consensus sequence (TGTAACG-N4-CGTTCCG) upstream of the gcs2 operon, consisting of the gcvH2, gcvP2, glyA2, sdaA, and gcvT2 genes. The proteins encoded by these genes, namely, the GCS (GcvH2-GcvP2-GcvT2), serine hydroxymethyltransferase (GlyA2), and serine dehydratase (SdaA), form a metabolic pathway for the conversion of glycine into pyruvate, which can enter the central metabolism. GcsR activates transcription of the gcs2 operon in response to glycine. Interestingly, GcsR belongs to a family of transcriptional regulators known as TyrR-like enhancer-binding proteins (EBPs). Until this study, TyrR-like EBPs were only known to function in regulating aromatic amino acid metabolism. GcsR is the founding member of a new class of TyrR-like EBPs that function in the regulation of glycine metabolism. Indeed, homologs of GcsR and its target genes are present in almost all sequenced genomes of the Pseudomonadales order, suggesting that this genetic regulatory mechanism is a common theme for pseudomonads. IMPORTANCE Glycine is required for various cellular functions, including cell wall synthesis, protein synthesis, and the biosynthesis of several important metabolites. Regulating levels of glycine metabolism allows P. aeruginosa to maintain the metabolic flux of glycine through several pathways, including the metabolism of glycine to produce other amino acids, entry into the trichloroacetic acid cycle, and the production of virulence factors such as hydrogen cyanide. In this study, we characterized GcsR, a transcriptional regulator that activates the expression of genes involved in P. aeruginosa PAO1 glycine metabolism. Our work reveals that GcsR is the founding member of a novel class of TyrR-like EBPs that likely regulate glycine metabolism in Pseudomonadales.

scholarly journals The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures.

1991 ◽  
Vol 266 (5) ◽  
pp. 3323-3329 ◽  
Author(s):  
A Kume ◽  
H Koyata ◽  
T Sakakibara ◽  
Y Ishiguro ◽  
S Kure ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Protein Structures ◽  
Glycine Decarboxylase ◽  
Glycine Cleavage System ◽  
Glycine Cleavage

scholarly journals Crystal structure of a component of glycine cleavage system: T-protein from Pyrococcus horikoshii OT3 at 1.5 Å resolution

2004 ◽  
Vol 58 (3) ◽  
pp. 769-773 ◽  
Author(s):  
Neratur K. Lokanath ◽  
Chizu Kuroishi ◽  
Nobuo Okazaki ◽  
Naoki Kunishima
Keyword(s):  
Crystal Structure ◽  
Glycine Cleavage System ◽  
Pyrococcus Horikoshii ◽  
Glycine Cleavage

scholarly journals Genomic Insights Into the Lifestyles of Thaumarchaeota Inside Sponges

2021 ◽  
Vol 11 ◽  
Author(s):  
Markus Haber ◽  
Ilia Burgsdorf ◽  
Kim M. Handley ◽  
Maxim Rubin-Blum ◽  
Laura Steindler
Keyword(s):  
The Novel ◽  
Glycine Cleavage System ◽  
Free Living ◽  
High Affinity ◽  
Branched Chain Amino Acid ◽  
Glycine Cleavage ◽  
Microbial Symbionts ◽  
Host Sponge ◽  
Branched Chain ◽  
Sponge Symbionts

Sponges are among the oldest metazoans and their success is partly due to their abundant and diverse microbial symbionts. They are one of the few animals that have Thaumarchaeota symbionts. Here we compare genomes of 11 Thaumarchaeota sponge symbionts, including three new genomes, to free-living ones. Like their free-living counterparts, sponge-associated Thaumarchaeota can oxidize ammonia, fix carbon, and produce several vitamins. Adaptions to life inside the sponge host include enrichment in transposases, toxin-antitoxin systems and restriction modifications systems, enrichments previously reported also from bacterial sponge symbionts. Most thaumarchaeal sponge symbionts lost the ability to synthesize rhamnose, which likely alters their cell surface and allows them to evade digestion by the host. All but one archaeal sponge symbiont encoded a high-affinity, branched-chain amino acid transporter system that was absent from the analyzed free-living thaumarchaeota suggesting a mixotrophic lifestyle for the sponge symbionts. Most of the other unique features found in sponge-associated Thaumarchaeota, were limited to only a few specific symbionts. These features included the presence of exopolyphosphatases and a glycine cleavage system found in the novel genomes. Thaumarchaeota have thus likely highly specific interactions with their sponge host, which is supported by the limited number of host sponge species to which each of these symbionts is restricted.

scholarly journals Inhibition of glycine cleavage system by pyridoxine 5′‐phosphate causes synthetic lethality in glyA yggS and serA yggS in Escherichia coli

2019 ◽  
Vol 113 (1) ◽  
pp. 270-284 ◽  
Author(s):  
Tomokazu Ito ◽  
Ran Hori ◽  
Hisashi Hemmi ◽  
Diana M. Downs ◽  
Tohru Yoshimura
Keyword(s):  
Escherichia Coli ◽  
Synthetic Lethality ◽  
Glycine Cleavage System ◽  
Glycine Cleavage

scholarly journals Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia

2008 ◽  
Vol 84 (7) ◽  
pp. 246-263 ◽  
Author(s):  
Goro KIKUCHI ◽  
Yutaro MOTOKAWA ◽  
Tadashi YOSHIDA ◽  
Koichi HIRAGA
Keyword(s):  
Reaction Mechanism ◽  
Physiological Significance ◽  
Glycine Cleavage System ◽  
Glycine Cleavage
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